Disease relevance of Redeptin

• The difference between the sexes in the potency of fluspirilene and its greater potential to induce parkinsonism may be related to its lesser presynaptic and D1-dopamine receptor blocking properties [1].
• In recent years concern has been frequently expressed that a long-term treatment with fluspirilene 1.5 mg/week might induce tardive dyskinesia, yet there are no empirical data from controlled studies available [2].
• Dystonic dysphagia associated with fluspirilene [3].
• We found no difference between depot fluspirilene and other oral antipsychotics with regard to relapses or to the number of people leaving the study early [4].
• Though movement disorders (n=60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4) were found only in the fluspirilene group, there were no convincing data showing the advantage of oral chlorpromazine or other depot antipsychotics over fluspirilene decanoate [4].

Psychiatry related information on Redeptin

• In the fluspirilene group a positive correlation of age and psychotropic comedication with the total scores of the AIMS and the akathisia scale could be found, but there was no correlation between duration or continuity of treatment with fluspirilene and symptoms of tardive dyskinesia [2].
• Test therapy in the treatment of generalized anxiety disorders with low dose fluspirilene [5].

High impact information on Redeptin

• Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM [6].
• Penfluridol and fluspirilene inhibited basal, Ca2(+)- and TRH-stimulated expression of a fusion gene construct containing the 5'-flanking sequence of the rat PRL gene linked to the luciferase gene [7].
• The GH luciferase construct was only slightly responsive to R5417 and TRH; however, these responses were reduced by fluspirilene and nimodipine at concentrations of less than 1 microM [7].
• In addition, high affinity sites have been detected for fluspirilene in bovine aortic sarcolemmal vesicles, rat brain synaptic membranes, and GH3 rat anterior pituitary cell plasma membranes [8].
• Diphenylbutylpiperidine (DPBP) antipsychotics, including penfluridol and fluspirilene, potently and preferentially block T-type Ca2+ current in the rat medullary thyroid carcinoma 6-23 (clone 6) cell line [9].

Chemical compound and disease context of Redeptin

• Fluspirilene induced more parkinsonism than chlorpromazine, but less drowsiness, dizziness, and dry mouth [1].
• In each of the two groups 10 patients (6.9% of the fluspirilene group and 8.3% of the benzodiazepine group) showed abnormal involuntary movements, which corresponds to the incidence of spontaneous dyskinesia [2].

Biological context of Redeptin

• Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene [10].
• 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley [10].
• Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance [10].
• This switch-over was rated as very good in three patients (allocation to nursing family) and good in two patients on fluspirilene (Imap); it was also rated as good in one patient on fluphenazine decanoate and one on pipamperone [11].

Anatomical context of Redeptin

• In rats treated with fluspirilene for 65-80 days the metabolism of [3H] choline taken up by striatal synaptosomes was investigated [12].
• 1. Fluspirilene has been claimed to bind to a high affinity site in the calcium channel in skeletal muscle [13].
• Fluspirilene block of N-type calcium current in NGF-differentiated PC12 cells [14].

Associations of Redeptin with other chemical compounds

• A 4-week double-blind controlled clinical trial was carried out in which fluspirilene, an injectable diphenylbutylpiperidine neuroleptic given weekly, was compared to chlorpromazine in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation [1].
• High-affinity uptake of choline and choline acetyltransferase activity (ChAT) were measured in the striatum of rats treated for 45-60 days with haloperidol (1 mg/kg per os) and pimozide (1 mg/kg per os) daily and with fluspirilene (1 mg/kg i.m.) twice a week [12].
• The various compounds also displayed high to moderate occupancy of adrenergic alpha 1 receptors, except fluspirilene and ziprasidone [15].
• Pimozide and fluspirilene inhibited Ca(2+) influx and ABA-induced RAB18 expression [16].
• Inhibition of glutamate release by fluspirilene in cerebrocortical nerve terminals (synaptosomes) [17].

Gene context of Redeptin

• In vitro, all compounds, except the 'typical' antipsychotics haloperidol and fluspirilene, showed higher affinity for 5HT2A than for D2 receptors [15].
• 1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a long-acting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity [10].
• Conditioned medium also depresses AChE and blocks the development of A12 AChE (Swerts et al., Dev. Biol., 103 (1984) 230-234), but these effects were insensitive to fluspirilene [18].
• The induction of the vesicular monoamine transporter by high K+ was dependent upon Ca2+ entry through slow calcium channels since it was inhibited by the diphenylbutylpiperidine antagonist fluspirilene and by 20 mM Mg2+, and was enhanced by the dihydropyridine agonist, Bay K8644 [19].
• Patients with psychosomatic complaints of a hypochondriacal nature were treated with a weekly IM dose of 1.2-1.5 mg fluspirilene (0.6-0.75 ml IMAP) for a period of 10 weeks [20].

Analytical, diagnostic and therapeutic context of Redeptin

• A controlled clinical trial of fluspirilene, a long-acting injectable neuroleptic, in schizophrenic patients with acute exacerbation [1].
• In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity [10].
• We describe a patient with fluspirilene-induced tardive dyskinesia of the choreiform oro-facial-laryngeal type resistant to various conservative approaches for 7 years who underwent deep brain stimulation of the internal pallidal globe [21].
• 1. The present double-blind study was designed to determine under three different conditions (0.5 mg, 1.0 mg, 1.5 mg per week) whether response or non-response within a two-week test-therapy predicts clinical outcome after 6 weeks of fluspirilene treatment in generalized anxiety disorders [5].
• Fluspirilene proved to be a very useful drug in the basic maintenance therapy of 21 chronic schizophrenic patients (ages 16-71 years), who received individually adjusted doses weekly during their hospitalization and during the subsequent follow-up period [22].

References